The long range goal of the research is to develop new, highly active drugs to treat important AIDS-associated opportunistic pathogens, including the intestinal protozoan parasite Cryptosporidium parvum and the fungal pathogens Pneumocystis carinii, Candida albicans and Cryptococcus neoformans. SBIR Phase I studies have identified a lead candidate drug, 2DPA 092, which is highly active orally in a neonatal mouse model of cryptosporidiosis, has excellent intravenous activity in a rat model of P. carinii pneumonia with reduce toxicity compared to the currently used drug pentamidine, and is also active against C. albicans and C. neoformans. No drugs with clinically proven efficacy are currently available to treat the devastating diarrhea of cryptosporidiosis in immunocompromised individuals. Therefore, the immediate goal of the research is to obtain sufficient preclinical data to apply for FDA approval to begin human clinical trials of 2DAP 092 as an orally active agent to treat cryptosporidiosis. The specific aims of this Phase II SBIR proposal are to synthesize sufficient quantities of 2DAP 092 to perform formal preclinical toxicity studies and further pharmacokinetic and ADME studies required to support to IND filing for Phase I clinical trials. PROPOSED COMMERCIAL APPLICATION The development of novel broad spectrum drugs, with improved efficacy, decreased toxicity and improved oral bioavailability, would be a valuable treatment for AIDS-related opportunistic infections, which account for the majority of the morbidity and mortality of patients. The development of any drug clinically active against Cryptosporidiosis is particularly needed.